Acoustic mixing for auto granulation

Patent metadata

Field	Value
Publication number	US-9949973-B2
Application number	US-201615204217-A
Country	US
Kind code	B2
Filing date	Jul 7, 2016
Priority date	Jul 7, 2015
Publication date	Apr 24, 2018
Grant date	Apr 24, 2018

Abstract

A process for acoustically mixing a bulk drug substance involves the application of acoustic energy to drive an accelerative force in a mixing vessel containing the drug substance. The drug substance may be, for example, Elagolix.

First claim

The invention claimed is:

1. A process comprising acoustically mixing a bulk drug substance consisting of at least 90% w/w drug substance and no more than 10% w/w of a pharmaceutical excipient or other material wherein said acoustic mixing comprises applying acoustic energy to a mixing vessel containing the drug substance for a time and at an intensity sufficient to form a granule.

2. The process according to claim 1 wherein an accelerative force of greater than 10 G is applied to the mixing vessel.

3. The process of claim 2 wherein said accelerative force is greater than 20 G.

4. The process of claim 3 wherein said accelerative force is greater than 40 G.

5. The process of claim 4 wherein said accelerative force is greater than 60 G.

6. The process of claim 5 wherein said accelerative force is greater than 80 G.

7. The process according to claim 1 wherein said drug substance comprises an amorphous solid.

8. The process according to claim 1 wherein said drug substance has a flowability constant of less than 5.

9. The process according to claim 1 wherein said drug substance has a flowability constant of less than 2.

10. The process according to claim 1 wherein prior to acoustic mixing, the drug substance has a flowability constant of less than 2 and subsequent to mixing greater than 2.

11. The process according to claim 1 wherein prior to acoustic mixing, the drug substance has a flowability constant of less than 1 and subsequent to mixing greater than 1.

12. The process according to claim 1 wherein the flowability constant is increased by at least 0.1.

13. The process according to claim 1 wherein the flowability constant is increased by at least 0.2.

14. The process according to claim 1 wherein the flowability constant is increased by at least 0.3.

15. The process according to claim 1 wherein the flowability constant is increased by at least 0.4.

16. The process according to claim 1 wherein the flowability constant is increased by at least 0.5.

17. The process according to claim 1 wherein prior to acoustic mixing said drug substance has a bulk density of less than 0.4 g/ml.

18. The process according to claim 1 wherein prior to acoustic mixing, the drug substance has a volume-averaged particle size DV10 of less than 100 μm.

19. The process according to claim 1 wherein acoustic mixing of the drug substance increases the volume-averaged particle size DV10 by at least 10 μm.

20. The process according to claim 1 wherein said drug substance is elagolix or elagolix monosodium salt.

21. A process comprising acoustically mixing a bulk drug substance consisting of at least 90% elagolix monosodium salt and no more than 10% of a pharmaceutical excipient or other material, wherein said acoustic mixing comprises applying acoustic energy to a mixing vessel containing the bulk drug substance for a time and at an intensity sufficient to produce a granule.

22. A granule comprising elagolix monosodium salt prepared by the process according to claim 21 .

23. A pharmaceutical formulation comprising the granule of claim 22 .

24. A process comprising acoustically mixing a bulk drug substance consisting of at least 90% amorphous elagolix monosodium salt and no more than 10% of a pharmaceutical excipient or other material, wherein said acoustic mixing comprises applying acoustic energy to a mixing vessel containing the bulk drug substance for a time and at an intensity sufficient to produce a granule.

25. A granule comprising elagolix monosodium salt prepared by the process according to claim 24 .

26. A pharmaceutical formulation comprising the granule of claim 25 .

Assignees

• Abbvie Inc

Inventors

• Gao Ping X
• Ho Raimundo
• Jayanth Jayanthy
• Mukherjee Samrat
• Peterson Katherine E
• Strong John C
• Tong Ping
• Zhang Geoff G

Classifications

• B01F2215/0032

  Operations & Transport · mapped topic

• A61J3/02

  into the form of powders (pulverising in general B02C) · CPC title

• B01F11/02

  Operations & Transport · mapped topic

• A61K31/505 Primary

  Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim · CPC title

• A61K9/1688 Primary

  resulting in pure drug agglomerate optionally containing up to 5% of excipient · CPC title